Cognitive impairment in lupus linked to 'abnormalities' in brain functional connectivity
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Patients with systemic lupus erythematosus who have cognitive impairment demonstrate abnormal brain functional connectivity relative to patients without impairment and healthy controls, according to data presented at ACR Convergence 2021.
“Cognitive impairment is frequent in SLE patients and fluctuates over time, suggesting reversable, central nervous system dysfunction,” John Hanly, MD, of Dalhousie University, in Halifax, Canada, told attendees at the virtual meeting. “Structural brain abnormalities have weak associations with cognitive impairment in SLE patients.”
“Functional MRI is an alternative neuroimaging approach that provides an indirect measure of neuron activity based on blood-oxygen level dependent, or BOLD, signals,” he added. “Structural MRI can assess regionally restricted brain function during execution of a specific task, or more generalized spontaneous brain function in a task-free, or so-called resting, state.”
To examine the link between functional brain abnormalities and cognitive impairment among those with SLE using resting-state functional MRI, and to analyze the association between these findings and blood-brain barrier permeability, Hanly and colleagues studied patients at a single academic medical center. Participants included 78 patients with SLE and 71 healthy control individuals. Cognitive impairment in those with SLE was defined based on global cognitive function assessment and performance in five individual cognitive domains, all using standard neuropsychological tests.
Meanwhile, the researchers quantitively assessed blood-brain barrier permeability in patients with SLE using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). All participants underwent resting-state functional MRI, in which BOLD signals were collected to indirectly assess neural activation.
Hanly and colleagues obtained mean BOLD signals from 131 regions of the brain across five canonical resting-state networks, and analyzed the resting-state functional connectivity between the regions. The researchers then compared resting-state functional connectivity values between those with SLE and healthy controls, as well as between those with and without extensive blood-brain barrier permeability among patients with SLE.
According to the researchers, among patients with SLE, 51 connections between functional brain regions differed between those with and without cognitive impairment (P < .05). A multivariate analysis of variance additionally showed differences between healthy controls and patients with both SLE and cognitive impairment (P = .006).
Among patients with SLE and cognitive impairment, within-network connectivity was significantly different for the sensory, attention/executive and language memory networks. The between-network connectivity differences occurred largely between the sensory and attention/executive networks, as well as between the default-mode and language-memory networks.
In addition, among patients with SLE, the mean functional connectivity of the impacted regions was different between those with normal blood-brain barrier permeability and those with extensive barrier leakage (P = .025). Patients with SLE and cognitive impairment, as well as those with extensive blood-brain barrier leakage, demonstrated more positive functional connections compared with the other groups.
Lastly, the total number of brain-wide connections of specific brain regions decreased with higher blood-brain barrier permeability (P = .011) and was lower in patients with both SLE and cognitive impairment than in those with SLE but without cognitive impairment (P = .01).
“SLE patients with cognitive impairment have abnormalities in brain functional connectivity,” Hanly said. “Reduced negative functional connectivity may indicate a compensatory response by some networks to overcome dysfunction in the default mode network.”
“The same abnormalities were seen in SLE patients with extensive blood-brain barrier leakage supporting the association with cognitive impairment,” he added. “Future studies should investigate the mechanisms underlying blood-brain barrier-mediated cognitive impairment and the potential of targeting the blood-brain barrier as a therapeutic strategy in SLE patients.”
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Hanly J. Abstract 0456. Presented at: ACR Convergence 2021; November 5-9, 2021 (virtual meeting).
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